Matrix metalloproteinases (MMPs) and the closely related ADAM (a disintegrin and metalloproteinase domain) and ADAMTS (a disintegrin and metalloproteinase domain with thrombospondin motifs) are soluble or membrane-anchored proteolytic enzymes that can degrade components of the extracellular matrix (ECM) as well as a growing numbers of modulators of cell functions. Our knowledge about the multifaceted contribution of these enzymes in all steps of cancer progression is rapidly expanding. The functional exploration of these cancer-associated enzymes led to a change in the way we view cancer and particularly the tumor-host interface. Several of these enzymes are produced by fibroblastic cells infiltrating the tumor rather than by tumor cells themselves, and therefore might be considered as key molecular determinants of the tumor microenvironment. In this review, we explore the different faces of fibroblastic-associated MMPs and ADAMTSs.